tbuckley/cabot-search huggingface dataset:
Neurosurgical morbidity in pediatric supratentorial midline low-grade glioma: Results from the German LGG studies.
Authors: Michèle Simon, Sarah Weiß, Ulrich-Wilhelm Thomale, Matthias Schulz, Daniela Kandels, Martin Schuhmann, Ahmed ElDamaty, Juergen Krauss, Pablo Hernáiz Driever, Olaf Witt, Brigitte Bison, Torsten Pietsch, Gnekow Astrid
Journal: Journal of Clinical Oncology (2023)

10044 Background: Surgical resection is a mainstay of treatment for pediatric low-grade glioma (LGG) within all current therapy algorithms, yet associated morbidity is scarcely reported. As supratentorial midline (SML) interventions are particularly challenging, we investigated the frequency of neurosurgical complications/new impairments aiming to identify their risk factors. Methods: Records were retrospectively analyzed from 318 patients with SML-LGG from successive German multicenter LGG studies, undergoing surgery between May 1998 and June 2020. Results: 537 operations (230 resections, 167 biopsies, 140 non-tumor procedures) were performed in 318 patients (54% male, median age: 7.6 years at diagnosis, 9.5 years at operation, 11% NF1, 42.5% optic pathway glioma). Surgical mortality rate was 0.93%. Applying the Drake classification, postoperative surgical morbidity was observed in 254/537 (47.3%) and medical morbidity in 97/537 (18.1%) patients with a 40.1% 30-day persistence rate for newly developed neurological deficits (65/162). Neuroendocrine impairment affected 53/318 patients (16.7%), visual deterioration 34/318 (10.7%). Postsurgical morbidity was associated with patient age &lt;3 years at operation, tumor volume ≥80cm 3 , presence of hydrocephalus, complete resection, surgery in centers with less than median reported tumor-related procedures and during the earlier study period between 1998-2006, while the neurosurgical approach, tumor location, NF1 status or previous non-surgical treatment were not. Conclusions: Neurosurgery-associated morbidity was frequent in pediatric patients with SML-LGG undergoing surgery in the German LGG-studies. We identified patient- and institution-associated factors that may increase the risk for complications. We advocate that local multidisciplinary teams consider the planned extent of resection and surgical skills. [Table: see text]
First line (1L) durvalumab in patients with PD-L1 positive, advanced non-small cell lung cancer (NSCLC) with a performance status of 2 (PS2): Primary analysis of the multicenter, single-arm phase II trial SAKK 19/17.
Authors: Michael Thomas Mark, Patrizia Froesch, Katrin Gysel, Sacha Rothschild, Alfredo Addeo, Christoph J. Ackermann, Sabrina Chiquet, Martina Schneider, Karin Ribi, Angela Fischer Maranta, Sara Bastian, Roger Anton Fredy Von Moos, Markus Joerger, Martin Früh
Journal: Journal of Clinical Oncology (2023)

9088 Background: The safety and efficacy of 1L durvalumab in PS2 patients (pts) with advanced NSCLC is unknown. Important safety data leading to exclusion of pts with relevant respiratory symptoms have been published as an interim report. Here we present the primary analysis of 1L durvalumab in PS2 pts, unsuitable for combination chemotherapy and PD-L1 expression in ≥25% of tumor cells. Methods: In this single-arm, multicenter, phase II trial pts with PD-L1 positive (tumor proportional score, TPS ≥25%), advanced NSCLC with PS2, unsuitable for combination chemotherapy determined by the investigators, in the absence of known contraindications for immunotherapy and sufficient organ function, received a fixed dose of 1500 mg durvalumab every four weeks. The primary endpoint was overall survival (OS) at 6 months. The statistical hypothesis was to improve OS at 6 months from ≤35% to ≥53%. Adverse events (AEs) were assessed according to National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) version 5.0. Results: Forty-eight pts were included (29 males, 19 females). Median age was 76 years (range, 37-87). OS at 6 months was 60% (95% CI: 45-74%). OS at 6 months after the exclusion of pts with initially relevant respiratory symptoms was 67% (95% CI: 46-84%, n = 27) compared to the subgroup of pts without this exclusion criteria who were recruited before the amendment (52%, 95% CI: 30-74%, n = 21). Median OS was 8.5 months (95%CI: 4.4-16.7). Objective response rate and median PFS were 17% (95% CI: 8-30%) and 2.5 months (95% CI: 1.8-7.1). Thirty-three deaths (69%) were observed to date. Ten early fatal events considered not treatment-related occurred during the first 5 weeks of treatment. Four out of the first 7 early fatal events (4/7; 57%) were respiratory failures in pts with advanced symptomatic primary lung tumors. Only 3 more early fatal events occurred after the protocol amendment excluding pts with severe respiratory symptoms. Thirty-nine patients (81%) had an AE grade ≥3 (G3). The most frequent AEs ≥G3 were lung infection (19%), dyspnea (15%) and hypertension (10%), respectively. Treatment-related AEs ≥G3 were reported in 9 pts (19%) and included colonic perforation in one patient (grade 5), colitis in 5 pts (10%), hepatitis and increased lipase in 3 pts each (6%). Conclusions: 1L durvalumab in PS2 pts with advanced PD-L1 positive (TPS ≥25%) NSCLC is effective and led to a promising 6-month OS of 60%. Four-weekly durvalumab can be safely offered to pts presenting without severe pulmonary symptoms who are not candidates for chemotherapy. Clinical trial information: NCT03620669 .
Association of COVID-19 pandemic with indolent lymphoma care delivery and outcomes in Ontario, Canada: A population-based analysis.
Authors: Michael Crump, Inna Y. Gong, Zharmaine Ante, Andrew Calzavara, Matthew Cheung, Anca A. Prica
Journal: Journal of Clinical Oncology (2023)

e18800 Background: Due to concern for infection risk, the coronavirus disease 2019 (COVID-19) pandemic presented a unique challenge for optimal management of indolent non-Hodgkin lymphoma (iNHL). We examined treatment (trt) selection, healthcare utilization, and COVID-19 outcomes of pts with iNHL receiving first-line (1L) systemic treatment during pre-pandemic vs. pandemic period. Methods: We performed a retrospective cohort study using administrative databases in Ontario, Canada, comparing outcomes in pts with iNHL who initiated trt from, with end of follow-up Mar 31 2022. The primary outcome was trt pattern (eg, 1L regimen, rituximab [R] maintenance use); secondary outcomes were death, toxicities, healthcare utilization (emergency department visit [ED], hospitalization), SARS-CoV-2 outcomes (infection, ED visit, hospitalization/death). Adjusted hazard ratios (aHR) from cause-specific proportional hazards models were used to estimate associations between factors and outcomes. Results: We identified 4,143 pts (1,079 pandemic, 3,064 pre-pandemic), median age 69 yrs, 44% female. In both pre- and pandemic periods, bendamustine (B)+R was the most frequent prescribed regimen, with no difference in number of cycles or dose delays (Table). During the pandemic, fewer pts received R maintenance and completed the full course (aHR 0.81, 95% confidence interval [CI] 0.71-0.92, p = 0.0010) (Table). Pts treated during the pandemic had less healthcare utilization (ED visit aHR 0.77, 95% CI 0.68, 0.88, p &lt; 0.0001; hospitalization aHR 0.81, 95% CI 0.70-0.94, p = 0.0067) and trt-related complications (infection aHR 0.69, 95% CI 0.57-0.82, p &lt; 0.0001; febrile neutropenia aHR 0.66, 95% CI 0.47-0.94, p = 0.020), with no difference in death (aHR 0.79, 95% CI 0.58-1.08, p = 0.14). R use (first dose to 1 yr post last dose) was associated with higher risk of SARS-CoV-2 infection (aHR 1.56, 95% CI 1.09-2.24, p = 0.015) and COVID-19 complications (ED visit aHR 4.28, 95% CI 1.79-10.26, p = 0.0011; hospitalization/death 1.81, 95% CI 1.11-2.93, p = 0.016). Conclusions: During the pandemic, BR remained the preferred regimen for iNHL trt, while R maintenance use was less. Despite the similar 1L regimen, healthcare utilization and infectious complications were less in the pandemic cohort. R use was associated with nearly 2-fold risk of COVID-19 hospitalization/death. [Table: see text]
Prognostic stratification and outcome of metastatic NSCLC based on activating mutation profile and PD-L1 status.
Authors: Kok Hoe Chan, Arthi Sridhar, Ji Zheng Lin, Syed Hasan Raza Jafri
Journal: Journal of Clinical Oncology (2023)

e18776 Background: The development of mutation-directed therapy and immunotherapy has revolutionized the treatment of NSCLC. We investigated outcomes of patients with or without actionable mutations (AM) in relation to their PDL-1 status. Methods: This was a retrospective analysis of patients with stage IV NSCLC from 01/2014 to 06/2022 at our institution. Four groups were identified: P0M0 (PDL-1 &lt;1% and no AM), P0M1 (PDL-1 &lt;1% with AM), P1M0 (PDL-1 ≥1% and no AM), and P1M1 (PDL-1 ≥1% with AM). X 2 and Wilcoxon rank-rum test were used to assess categorical and continuous data, respectively. Progression-free survival (PFS) and overall survival (OS) were compared between groups using the Cox proportional-hazards model. Results: A total of 117 patients were included. Median age was 65 years, and 63 (54%) were male. The most common histology was adenocarcinoma (79%), followed by squamous cell cancer (14%) and large cell carcinoma (4%). The most common AM was KRAS (22%), followed by EGFR (21%), MET (4%), and HER2 (4%). The median PFS and OS of the entire group were 11.8 and 33.5 months, respectively. Adenocarcinomas had a higher incidence of harboring an AM (62%, p&lt;0.0001). When comparing the PFS and OS with regard to PDL-1 and an actionable mutation, 4 prognostic groups were identified (Table). The P0M0 subgroup (n=24) had the worst median PFS and OS (8.5 and 20.6 months). The P1M1 subgroup (n=41) had the best OS at 44.5 months. Patients in the P0M1 subgroup had a longer PFS than those in the P1M1 subgroup (25.2 vs. 13.1 months), likely due to the presence of more EGFR mutations (57% vs. 32%, p=0.05). However, this did not translate into improved OS (P0M1: 33.5 months, P1M1: 44.5 months, log-rank p=0.98), perhaps because of the durable long-term response to immunotherapy in patients with PDL-1 ≥1%. The results were not significant, likely due to the small sample size in each category. Conclusions: Patients with PDL-1 &lt;1% and no AM had the worst prognosis (median OS, 20 months). Patients with AM and PDL-1 ≥1% had the best OS, 44.5 months. This use of real-world data is an important addition to the existing information to predict survival outcomes of patients with stage IV NSCLC based on the current treatment paradigm. It provides important clinical information and should be corroborated in a larger study. [Table: see text]
Clinical outcomes of chemotherapy rechallenge in patients with metastatic non-small cell lung (NSCLC) who progressed on immunotherapy maintenance after front line platinum doublets and immunotherapy.
Authors: Kaiwen Wang, Frank V. Fossella, Marcelo Vailati Negrao, Tina Cascone, Carl Michael Gay, Xiuning Le, Natalie I Vokes, Celyne Bueno Hume, Amy Aida Hassan, Don Lynn Gibbons, J. Jack Lee, John Heymach, Jianjun Zhang
Journal: Journal of Clinical Oncology (2023)

e21205 Background: Maintenance immunotherapy (IO) is commonly utilized in metastatic NSCLC patients (pts) who did not progress after initial treatment with platinum doublet and IO. Upon progression, docetaxel with or without ramucirumab remains the treatment of choice, which is associated with poor response and high toxicity. We explored the option of rechallenge of original chemotherapy agents in this patient population. Methods: We queried MD Anderson Cancer Center GEMINI database to perform a retrospective review in pts who received chemotherapy (chemo) rechallenge with or without IO after progression on or after IO maintenance from 03/2016 – 12/2022 at MD Anderson Cancer Center. We assessed clinical response and progression free survival (PFS) with initial triplet treatment and rechallenge with chemotherapy. Clinical response was defined as clinical benefit based on clinician’s radiographic and clinical assessment. PFS was defined as the time interval free of disease progression. Demographics and results were summarized with descriptive statistics. Results: 20 patients received chemo rechallenge with or without IO after progression on IO maintenance. Upon chemo rechallenge, 7 pts received pemetrexed; 10 pts (50%) received carboplatin and pemetrexed; 19 pt received chemo rechallenge with IO. Median duration of initial IO maintenance was 9.4 months. Median duration of chemo rechallenge was 5.2 months. 10 (50%) pts discontinued chemo due to progression after receiving chemo rechallenge; 2 (10%) pts discontinued chemo rechallenge due to toxicities; 3 (15%) pts remained on therapy at the data cutoff of 2/10/2023. Median PFS with initial triplet was 14.3 months. Median PFS with chemo rechallenge was 7.4 months, longer than the histological control of 3-5 months from docetaxel +/- ramucirumab. Conclusions: Our single center retrospective review demonstrated that chemo rechallenge after progression on IO maintenance post front-line chemo-IO therapy had good tolerability and reasonable PFS, which may offer a reasonable alternative option to docetaxel+/-ramucirumab. Future studies are needed to confirm this result using docetaxel +/- ramucirumab as a control. [Table: see text]
Engagement of patient participation in genomics research by the Osteosarcoma and Leiomyosarcoma Count Me In Projects of the Cancer Moonshot funded PE-CGS Network.
Authors: Suzanne George, Diane Diehl, Carrie Cibulskis, Priscilla Merriam, Maeve Smart, Jordan Doucette, Elana Anastasio, Benjamin Zola, Ashley Matthews, Evelina Ceca, Noorshifa Arssath, Lorena Lazo De La Vega, Sidney Benich, Ellen Sukharevsky, Sarah Winnicki, Lauren Fisher, Brendan Michael Reardon, Eliezer Mendel Van Allen, Jennifer W. Mack, Katherine A. Janeway
Journal: Journal of Clinical Oncology (2023)

TPS11588 Background: Osteosarcoma (OS) and Leiomyosarcoma (LMS) are sarcomas with complex genomes for which there has been limited progress in identifying new treatments and improving outcomes. Slow progress in OS and LMS is partially due to insufficient characterization of the genomic landscape. Generating large genomic datasets in OS and LMS is challenging because of the rarity of these sarcomas and recruitment barriers such as care fragmentation between institutions and specialties. The OS and LMS Project research studies aim to: 1) establish a network of engaged pediatric and adult participants with OS and LMS who will co-create a shared database of clinical, genomic, molecular, and patient reported data to enable research; 2) define the clinicogenomic landscape of OS and LMS; and 3) optimize the approach to direct patient engagement in cancer research. Methods: Count Me In, a research initiative with prior success in angiosarcoma, working with patients and advocates created websites (OSProject.org and LMSProject.org) where patients register and consent to participation. Projects were launched in September, 2022. After 5 months of accrual, 306 patients age 6-79 from 149 Institutions have consented. Blood and saliva are collected from consented participants, tumor samples are obtained from pathology departments and medical records are requested from treating hospitals. WES and WGS of tumor and normal, and RNASeq of tumor is performed. ctDNA is obtained and sequenced. Results are shared with patient, advocacy, physician and research communities in several ways. Individual participants receive a shared learning report describing the somatic variants identified in their tumor from paired tumor-normal WES and are offered genetic counseling and clinical germline testing. Registered participants receive updates via email and Project websites. There are regular pre-publication data releases to the genomic data commons and to cBioPortal. A physician engagement committee meets regularly to discuss clinical insights and conundrums from shared learning reports and germline testing. Patient accrual over the next 3 years is anticipated to result in sequencing of 750 tumor-normal pairs and 500 ctDNA samples.
Did COVID-19 impact national trends of hospitalization and outcomes for neutropenic fever in adults with cancer?
Authors: Prarthna V Bhardwaj, Lekha Yadukumar, Ishani Patel, Deepak Pasupula, Chandravathi Loke, Kathan Mehta, Sudeep Kumar Siddappa Malleshappa
Journal: Journal of Clinical Oncology (2023)

e18799 Background: Neutropenic fever (FN) is an oncologic emergency associated with significant morbidity and mortality. Patients on chemotherapy are at a higher risk of COVID-19-related complications. During the initial phase of the pandemic, healthcare systems were overwhelmed, resulting in shortage of resources and rationing of care. We aimed to assess the impact of the COVID-19 on trends of hospitalization and outcomes in adult emergency department (ED) visits for cancer-related FN in the US between 2019 and 2020. Methods: In this retrospective observational study using the National Emergency Department Sample of adults presenting to ED for cancer-related FN as primary diagnosis (using ICD-10-CM codes), we compared the outcomes between patients presenting in 2019 (pre-pandemic) and 2020. The primary outcome was mortality. Secondary outcomes were incidence of shock, discharge disposition, and length of stay (LOS). A propensity score matching was performed to estimate the effect of COVID-19 on outcomes. Results: There were a total of 95,163 visits to the ED for FN in 2019 and 2020. Both groups had similar demographics, with mainly White (68.1% vs 69.3%) patients presenting to large metropolitan areas (57.6% vs 58.6%) and mostly metropolitan teaching hospitals (74.5% vs 77.2%). More patients presenting in 2020 had a higher Elixhauser comorbidity index (66.6% vs 70.2% for comorbidity of ≥3; p = 0.0002). Although the number of patients who got admitted or died in the ED was similar in 2019 and 2020 (88.4% vs 87.8% for admission and 0.1% for death, p = 0.83), higher number died during their hospitalization (3.4% vs 4.4%, p = 0.002), and were likely to develop shock (6.0 vs 7.1%, p = 0.005) in 2020. More patients were discharged home with services (21.9% vs 17.1%, p &lt; 0.001), while fewer patients went to nursing homes (7.9% vs 8.5%, p &lt; 0.001) in 2020. There were no significant differences in LOS or cost of hospitalization. A propensity score matching was performed to estimate the effect of COVID-19 on outcomes showing higher mortality during hospitalization (13.7% vs 4.6%, p = 0.006) and increased LOS (6 days vs 5 days, p = 0.02) for patients with concurrent COVID-19. Conclusions: Overall, mortality related to FN was higher during the pandemic and more so among patients with concurrent COVID-19. While patients developing shock was higher in 2020, this was not attributable to COVID. Fewer patients were discharged to nursing homes, and more patients went home with services during the pandemic highlighting the constraints imposed on resources during the pandemic. [Table: see text]
Co-mutational status and PD-L1 expression in <i>KRAS</i> mutant non-small cell lung cancer (NSCLC): Role in treatment selection and association with clinical outcomes.
Authors: Hina Khan, Julia Judd, Joanne Xiu, Asad Ullah, Girindra Ghanshyam Raval, Patrick C. Ma, Jorge J. Nieva, Milan Radovich, Matthew James Oberley, So Yeon Kim, Hirva Mamdani, Luis E. Raez, Ari M. Vanderwalde, Balasz Halmos, Hossein Borghaei, Stephen V. Liu, Nagla Fawzy Abdel Karim
Journal: Journal of Clinical Oncology (2023)

9038 Background: In NSCLC, different KRAS mutations (mt) define unique subgroups and certain co-mutations (co-mt) could have prognostic and therapeutic implications. Retrospective studies associate poor prognosis with co-mts in STK11 and KEAP1 with KRAS. It is unclear if PD-L1 expression and co-mt in KRAS mt NSCLC impacts outcomes. Methods: Molecular profiles of 27748 NSCLC tumors were tested with next-generation sequencing (Caris Life Sciences, Phoenix, AZ) and classified by KRAS mt. PD-L1 IHC (22C3) was reported as TPS. Real-world post-immunotherapy (IO) overall survival (OS) was obtained from insurance claims and calculated from start of an immune check-point inhibitor (with or without chemotherapy) to the last day of follow-up. Results: In all, 7634 (28%) samples had a KRAS mt; most common being G12C (11%), G12V (5.3%), G12D (3.9%) and G13X (2.0%). The most frequent co-mt was KRAS-TP53 (KP) (46%), similar in all KRAS subtypes. KRAS-STK11(KL) was in 23% of KRAS mt, enriched in G13X (33%) and lowest in G12D (16%). KRAS-KEAP1(KK) was co-mt in 10% of KRAS mt, highest in G13X (16%) and lowest in G12D (8%). KRASmt/ STK11wt/ KEAP1wt/ TP53wt (K only) was 27% of KRAS mt, highest in G12D (36%) and lowest in G13X (16%). A small subgroup, 5.6% was KRAS-STK11-KEAP1 co-mt (KKL). The majority of pts in the KL (61%), KK (52%) and KKL (62%) cohorts had TPS &lt;1%. In 1723 KRAS mt NSCLC pts treated with IO, KL, KK and KKL had significantly worse post-IO OS than KP and K only (table); KKL had the lowest OS. In the TPS≥1% KRAS mt group, KL, KK and KKL had worse post-IO OS than KP and K-only. In TPS&lt;1% group, KL and KK had poor post-IO OS and K-only had favorable outcomes. However, KP had worse post-IO OS compared to K-only in TPS&lt;1%. In G12C and G12V, similar trend with worse post-IO OS in KL, KK and KKL, compared to KP and K only was noted. Conclusions: We report a large real-world dataset evaluating outcomes with check-point inhibitors in NSCLCs with KRAS and specific co-mts. KL, KK and KKL subgroups demonstrate universally poor outcomes in all KRAS subtypes irrespective of PD-L1. Pts with KP co-mts have adverse post-IO outcomes in TPS&lt;1% but favorable in TPS≥1%. TPS score remains a predictive marker of IO outcomes in KP, but not in KL, KK and KKL. These observations emphasize that both PD-L1 and co-mts have a clear association with clinical outcomes in KRAS-mt NSCLC, and must be used in predictive models for individualized therapy. [Table: see text]